NeoQuest August 2023: Fetal Complications in a Monochorionic Diamniotic Twin Pregnancy

A 30-year-old primigravida patient with a monochorionic diamniotic (MCDA) twin pregnancy complicated by stage IV twin-to-twin transfusion syndrome (TTTS) is being evaluated for endoscopic laser photocoagulation at 24 weeks’ gestation. Ultrasonography images of each twin are shown below.

Figure 1: Ultrasonography images of twin A (left panel, red circle) showing the location of the dividing membrane (red arrow) and twin B (right panel) showing scalp edema (yellow arrow). From: Conyers S, Young BC. Twin-twin transfusion syndrome in monochorionic diamniotic twins. Neoreviews. 2023;24(8):e522–525¹

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Explanation:

The ultrasonography image of twin A shows severe oligohydramnios. The dividing membrane is observed to have a “shrink-wrap” appearance around twin A due to low amniotic fluid volume (Figure 1, red arrow).¹ Part of Twin B can also be seen on the left panel (Figure 1, left of the red circle). In the context of TTTS, twin A is the donor twin, who is most likely to have oligohydramnios, increased middle cerebral artery Doppler waveforms, and hypoalbuminemia (Option A). Twin B’s head is shown with findings of scalp edema (Figure 1, yellow arrow). Twin B is the recipient twin and is more likely to have polyhydramnios, normal middle cerebral artery Doppler waveforms, and normal serum albumin (Option B).

TTTS is a complex and life-threatening condition that occurs in approximately 10%–20% of all monochorionic twin pregnancies.² A diagnosis of TTTS is based on ultrasonography confirmation of 1) the presence of monochorionicity and 2) concomitant oligohydramnios in the donor twin and polyhydramnios in the recipient twin.^2,3 TTTS is thought to be due to unbalanced placental vascular anastomoses that lead to an acute or chronic transfer of blood flow from  donor twin to recipient twin (Figure 2).^2-4 The donor twin experiences reduced blood volume while the recipient twin receives excessive amounts of blood. The two types of TTTS are twin oligo-polyhydramnios sequence (TOPS) and twin anemia-polycythemia sequence (TAPS). In TOPS, there is a difference in amniotic fluid volumes and hematocrit levels between the twins. In TAPS, there is a difference in fetal hematocrit levels and no difference in amniotic fluid volumes between the twins. The severity of TOPS is commonly categorized with a staging system proposed by Quintero et al. (Table 1).^1,5 The Quintero classification system helps clinicians identify pregnant people who may benefit from expectant management versus invasive therapy (eg, amnioreduction and fetoscopic laser photocoagulation).^6,7 The severity of TAPS is categorized by the intertwin hemoglobin difference.⁸ TTTS disease progression varies widely, and it is common for both upstaging and downstaging to occur at random.⁹ 



Figure 2: Diagram of the anastomoses of a monochorionic diamniotic gestation complicated by TTTS. The left umbilical cord is the recipient twin (I), and the right umbilical cord is the donor twin (II).  The arteries are shaded blue to represent relatively lower blood oxygenation, while the veins are shaded red to represent relatively higher blood oxygenation. Within the deep arteriovenous connections (yellow circle), an artery from the donor twin (II) supplies a portion of the chorionic villous tree that is drained by a vein from the recipient twin (I). From: Faye-Petersen O, Crombleholme T. Twin-to-twin transfusion syndrome: part 1. Types and pathogenesis. Neoreviews. 2008;9(9):e370–e379

Table 1. Twin-Twin Transfusion Syndrome Staging. From: Conyers S, Young BC. Twin-twin transfusion syndrome in monochorionic diamniotic twins. Neoreviews. 2023;24(8):e522–525. MVP: Maximum vertical pocket of amniotic fluid.

One diagnostic criterion of TTTS is the presence of oligohydramnios in the donor twin and polyhydramnios in the recipient twin.^2,3 The donor twin experiences decreased blood flow causing renal hypoperfusion, which activates the renin-angiotensin-aldosterone system (RAAS) and leads to oliguria.^4,10 Because fetal urine is the largest contributor to amniotic fluid during the second and third trimesters, amniotic fluid volumes decrease.¹¹ Conversely, the recipient twin experiences increased blood flow, leading to cardiac stretch, which increases atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Elevated ANP and BNP levels inhibit the RAAS and lead to the development of polyuria and polyhydramnios.^4,10 The amniotic fluid volume of Options B and C is incorrect because the increased amniotic fluid volume is more likely to occur in Twin B (recipient twin) and not Twin A (donor twin). Ongoing research is examining multiple other hormonal and physiologic mechanisms that have been implicated in the development of amniotic fluid discordance in TTTS.⁴

Middle cerebral artery (MCA) Doppler measurements are used to evaluate for fetal anemia.¹² By measuring the blood flow velocity in the MCA, the Doppler waveform pattern provides information about fetal blood flow characteristics (Figure 3A).¹² In fetal anemia, the MCA Doppler waveform shows signs of increased blood flow velocity due to decreased blood viscosity and increased cardiac output (Figure 3B).¹² In TTTS, the donor twin is more likely to have anemia and will thus show increased MCA Doppler velocity. In contrast, the recipient twin is more likely to have polycythemia. MCA Doppler velocity has not been shown to be significantly decreased in fetuses with polycythemia compared to normal controls and thus has limited utility in the diagnosis of fetal polycythemia. The MCA Doppler findings of Options B, C, and E are incorrect because a normal or decreased MCA Doppler velocity would not be seen in Twin A (donor twin).  Anemia in the donor twin is also a risk factor for hydrops fetalis. Anemia diminishes oxygen-carrying capacity, causing hypoxia, increased oxygen extraction, increased cardiac output, congestive heart failure, increased central venous pressure, and increased interstitial fluid accumulation.¹³ The recipient twin is also at risk for the development of hydrops fetalis due to congestive heart failure from hypervolemia.^4,14


Figure 3: (A) Fetal Doppler ultrasonography showing a Doppler waveform of normal MCA flow in contrast to a (B) waveform of increased MCA blood flow velocity above 1.5 multiples of the median. From: Taslimi M. Doppler ultrasonography in the assessment of fetal well-being. Neoreviews. 2004;5(6):e247–e251 and Clear E, Braginsky L,  Plunkett BA. Strip of the Month: A catastrophic fetal intracranial hemorrhage. Neoreviews, 2018;19(8):e493–e501

Anemia in the donor twin can lead to multiple complications, including hypoalbuminemia and hydrops fetalis.^9,15 The donor twin in TTTS has been shown to have marked hypoalbuminemia, most likely secondary to severe anemia.¹⁴ In a 2013 matched case-control study, hypoalbuminemia occurred frequently in donor twins treated conservatively.¹⁵ Serum albumin is typically normal in recipient twins and in donor twins after fetoscopic laser therapy.¹⁵ The decreased oncotic pressure caused by hypoalbuminemia may also put the donor twin at risk for the development of hydrops fetalis.¹⁵ The albumin levels referenced in Options B, C, and D are incorrect because Twin A (donor twin) is more likely to have hypoalbuminemia.

Fetoscopic laser occlusion of chorioangiopagous vessels (FLOC) is currently the gold-standard therapy for progressive and severe TTTS.⁹ FLOC is a minimally invasive procedure performed under ultrasonography guidance.⁹ A laser fiber is inserted into the uterus through a small incision and used to selectively coagulate the abnormal vascular anastomoses connecting the twins in the shared placenta (Figure 4).⁹ By “dechorionizing” a monochorionic placenta, FLOC can help restore the hemodynamic balance between twin fetuses and protect either fetus from vascular steal in the event of a co-twin demise.⁹


Figure 4: Illustration of fetoscopic surgery of monochorionic diamniotic twins with severe TTTS. Note that the donor twin (left) has oligohydramnios with a “shrink-wrap” appearance of the dividing membrane while the recipient twin (right) has polyhydramnios. (See Figure 1 for an ultrasonography image). The endoscope is inserted through the polyhydramniotic sac, and the laser beam is aimed to photocoagulate placental anastomoses between the two fetuses. From: Bliss J, Carr SR, De Paepe ME, Luks FI. What—and why—the neonatologist should know about twin-to-twin transfusion syndrome. Neoreviews. 2017;18(1):e22–e32 Image courtesy of Francois I. Luks, MD [CC BY-SA 3.0]

Did you know?

When there is a twin demise in chronic TTTS, the surviving twin has a 25%–30% risk of severe neurologic or cardiac anomalies.⁹

What advancements have been made in fetoscopic laser therapy for TTTS, and how have they affected fetal outcomes?

To find the answer, please refer to the following article: Olutoye OO, Joyeux L, King A, Belfort MA, Lee TC, Keswani SG. Minimally invasive fetal surgery and the next frontier. Neoreviews. 2023;24(2):e67–e83

NeoQuest August Authors:
Angelina June, MD, University of Virginia
Faith Kim, MD, Columbia University

References

1. Conyers S, Young BC.  Twin-twin transfusion syndrome in monochorionic diamniotic twins. Neoreviews. 2023;24(8):e522–525
2. Habli M, Lim FY, Crombleholme T. Twin-to-twin transfusion syndrome: a comprehensive update. Clin Perinatol. 2009;36(2):391–416
3. Simpson LL. Twin-twin transfusion syndrome. Am J Obstet Gynecol. 2013; 208(1):3–18
4. Faye-Petersen O, Crombleholme T. Twin-to-twin transfusion syndrome: part 1. Types and pathogenesis. Neoreviews. 2008;9(9):e370­–e379
5. Quintero RA, Morales WJ, Allen MH, Bornick PW, Johnson PK, Kruger M. Staging of twin-twin transfusion syndrome. J Perinatol. 1999;19:550–555
6. Quintero RA, Dickinson JE, Morales WJ, et al. Stage-based treatment of twin-twin transfusion syndrome. Am J Obstet Gynecol. 2003;188:1333–1340
7. Senat MV, Deprest J, Boulvain M, Paupe A, Winer N, Ville Y. Endoscopic laser surgery versus serial amnioreduction for severe twin-to-twin transfusion syndrome. N Engl J Med. 2004;351(2):136–144
8. Bliss J, Carr SR, De Paepe ME, Luks FI. What—and why—the neonatologist should know about twin-to-twin transfusion syndrome. Neoreviews. 2017;18(1):e22–e32
9. Slaghekke F, Kist WJ, Oepkes D, et al. Twin anemia-polycythemia sequence: diagnostic criteria, classification, perinatal management and outcome. Fetal Diagn. 2010;27(4):181–190
10. Borse V, Shanks AL. Twin-to-twin transfusion syndrome. StatPearls [Internet].. StatPearls Publishing. January 2023
11. Fitzsimmons ED, Bajaj T. Embryology, amniotic fluid, StatPearls [Internet]. StatPearls Publishing. January 2023
12. Taslimi M. Doppler ultrasonography in assessment of fetal well-being. 2004;5(6):e247–e251
13. Fishel-Bartal M, Weisz B, Mazaki-Tovi S, Ashwal E, Chayen B, Lipitz S, Yinon Y. Can middle cerebral artery peak systolic velocity predict polycythemia in monochorionic-diamniotic twins? Evidence from a prospective cohort study. Ultrasound Obstet Gynecol. 2016;48(4):470–475
14. Lorch SA, Mollen TJ. Nonimmune hydrops. In: Avery’s Diseases of the Newborn. Philadelphia, PA: Elsevier; 2018
15. Verbeek L, Middeldorp JM, Hulzebos CV, Oepkes D, Walther FJ, Lopriore E. Hypoalbuminemia in donors with twin-twin transfusion syndrome. Fetal Diagn Ther. 2013;33(2):98–102